Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV003234901 | SCV003932890 | likely pathogenic | not provided | 2022-12-15 | criteria provided, single submitter | clinical testing | Published functional studies of this variant demonstrated a damaging effect on FGD1 function with reduced activation of MLK3 and reduced Runx2-responsive OG2-luc activity (Zou et al., 2011); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 11093277, 21965325) |
Invitae | RCV003234901 | SCV004299568 | uncertain significance | not provided | 2023-10-03 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 522 of the FGD1 protein (p.Arg522His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Aarskog syndrome (PMID: 11093277). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 10826). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FGD1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
OMIM | RCV000011573 | SCV000031805 | pathogenic | Aarskog syndrome | 2000-11-01 | no assertion criteria provided | literature only |